The proposed program of projects is comprised of several investigations having overlapping interests and many common experimental approaches. The projects have similar objectives in their focus on the general area of mental retardation and other neurological diseases, seeking improved diagnostic procedures, new therapeutic measures, and elucidation of specific biochemical defects. The investigations encompass broadly the disciplines of biochemistry and genetics with specific projects ranging from basic to clinical in nature. The several projects encompass the areas of (1) pyrrole metabolism with studies of induced and inheritied abnormalities in heme biosynthesis especially relating to iron nutrition, lead intoxication, and the porphyrias, and studies of hyperbilirubinemia in newborn and infant Macaca nemestrina, (2) genetic aspects of amino acid metabolism and elucidation of the biochemical lesions in certain of these diseases, as well as lacticacidosis and Menke's disease, (3) the pathologic and metabolic aspects of the mucopolysaccharidoses with particular attention to new therapeutic measures, and (4) genetic and biochemical studies of the leukodystrophies.